Apoptosis induction in fludarabine resistant malignant B-1 cells by G2-M cell cycle arrest.
A malignant B-1 cell line from a mouse model of CLL was resistant to fludarabine, but could be induced to undergo apoptosis by mitotic spindle inhibitors, colcemid or nocodazole, which blocked these cells in the G2-M phases of cell cycle prior to apoptosis induction. Bax mRNA levels increased with relative constitutive expression of bcl-2 mRNA levels. The mRNA levels of B-cell-specific-activator-protein (BSAP) decreased with colcemid treatment. This study shows that mitotic spindle inhibitors can induce apoptosis in fludarabine-resistant malignant B-1 cells by altering levels of bax/ bcl-2 ratio and BSAP which play different roles in cell cycle regulation and apoptosis induction.
Zhang
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Department of Pathology and Laboratory Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
Raveche
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D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis; D001402:B-Lymphocytes; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D003703:Demecolcine / Q000633:toxicity*; D019008:Drug Resistance, Neoplasm; D016195:G2 Phase; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D051379:Mice; D008938:Mitosis; D009687:Nuclear Proteins / Q000096:biosynthesis; D051757:PAX5 Transcription Factor; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D008941:Spindle Apparatus / Q000187:drug effects; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000633:toxicity; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494827:Bax protein, mouse; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D014740:Vidarabine; C024352:fludarabine; D003703:Demecolcine